Cytokines Flashcards
Macrophages secrete which cytokines?
IL-1
IL-6
IL-8
IL-12
IL-18
Tumor necrosis factor-α
Transforming growth factor-β
IL-1 is mostly secreted by which cells?
Monocytes/ Macrophages
B cells
Dendritic cells
Endothelial cells
How does IL-1 affect Th cells?
Costimulation activation
IL-1 effect on B cells?
Promotes maturation & clonal expansion
IL-1 effect on NK cells?
↑ activity
IL-1 effect on endothelial cells
↑ ICAMs
intercellular adhesion molecules/ selectins
IL-1 effect on macrophages & neutrophils?
Chemotaxis (attracts them)
IL-1 effect on hepatocytes?
Induces synthesis of acute-phase proteins
IL-1 effect on hypothalamus?
Induces fever
Costimulation activation is caused by which interleukins?
IL-1
IL-4
IL-1 effect on bone?
Activates osteoclasts
Osteoclast-activating factor
IL-2 effect?
secreted by?
Adaptive immunity
- ↑ B cells
- ↑ activated T cells (↑helper ↑cytotoxic ↑Treg cells)
- ↑ NK cell function
(secreted by Th cells)
IL-3 effect?
secreted by?
Adaptive immunity
-Stimulates bone marrow: hematopoietic precursor proliferation and differentiation → ↑bone marrow stem cells
(function similar to GM-CSF; granulocyte macrophage colony stimulating factor)
(secreted by Th cells & NK cells)
IL-4 effect?
secreted by?
Humoral & Adaptive immunity & pro-inflammatory
- class switch to IgG & IgE
- Costimulation activation & ↑ B & T cells
- enhances MHC class II expression
- ↓Th1, ↓macrophages, ↓IFN-gamma, ↓IL-12
(secreted by Th2 cells, mast cells, eosinophils, basophils)
IL-5 effect?
secreted by?
Adaptive immunity
- IgM & Class switch to IgA
- Eosinophil activation
- B-cell proliferation and maturation
(secreted by Th2 cells & mast cells)
IL-6 effect?
secreted by?
Pro-inflammatory
- Induces acute-phase protein synthesis in hepatocytes
- Proliferating B cells → plasma cells → stimulates antibody secretion
- Promotes differentiation in myeloid stem cells
(secreted by monocytes/ macrophages, Th2 cells, bone marrow stromal cells, fibroblasts)
IL-6 effect on hepatocytes?
Induces acute-phase protein synthesis
Which cytokines are pro-inflammatory (cause fever)?
IL-1
IL-6
IL-8
IL-11
IL-17
IL-18
IFN-α/ IFN-β/ IFN-γ
TNF-α/ TNF-β
IL-8 effect?
secreted by?
Pro-inflammatory
- Neutrophil chemokine
(neutrophil & T cell chemotaxis: induces adherence to endothelium & extravasation into tissues to clear infection)
(secreted by macrophages & endothelial cells)
IL-12 effect?
secreted by?
Anti-inflammatory
- Activates NK cells
- Induces T cells → Th1 cells
- Facilitates granuloma formation in TB
- phagocyte cell activation
- endotoxic shock
- tumor cytotoxicity
- cachexia
(secreted by T cells, monocytes/ macrophages)
IL-1 effect?
secreted by?
Pro-inflammatory
- Pyrogenic
- ↑ B cells
- ↑ NK cells
- ↑ T-cells
- ↑ BM bone marrow cells
(secreted by Monocytes/ Macrophages, B cells, Dendritic cells, Endothelial cells)
Which cytokines are anti-inflammatory?
IL-10
IL-12
IL-22
IL-37, IL-38
TGF-β
Which cytokines are part of adaptive immunity?
IL-2, IL-3, IL-4, IL-5
IL-7
IL-9
GM-CSF
granulocyte macrophage colony stimulating factor
M-CSF
macrophage colony stimulating factor
What are the illnesses associated with IL-4?
Allergic inflammation
- allergic asthma
- atopic dermatitis
- allergic rhinitis
Tumors
- rhabdomyosarcoma
- meningiomas
HIV
IL-10 effects?
secreted by?
Anti-inflammatory
- ↓ MHC class II
- ↓ Th1 cytokines (IFN-γ)
- ↓ activated macrophages
- ↓ dendritic cells
(secreted by B cells, macrophages, Th2 cells, also Treg cells)
IL-13 effect?
secreted by?
Pro-inflammatory
(similar to IL-4 because shared receptor)
- ↑ IgE
- Induces alternative macrophage activation
- goblet cell hyperplasia
- mucus hypersecretion, airway hyperresponsiveness, fibrosis
(secreted by Th2 cells, CD4 cells, NK cell, mast cells, basophils, eosinophils)
IFN-γ effect?
secreted by?
Pro-inflammatory
- Anti-viral (↑ NK cells to kill virus)
- ↑ macrophage activation & maturation (formation of phagolysosome → kill phagocytosed pathogen & granuloma formation: CGD treatment)
- ↑ IgG (B cells)
- ↑ neutrophil and monocyte function
- ↑ MHC-I and -II expression on all cells
- iNOS inducible nitric oxide synthase (produces nitrogen intermediates & free radicals which destroy components of M.TB)
- ↓ Th2 cells
- ↓ blocks IL-4 switch to IgE
(secreted by NK cells & mature Th1 Cells in response to
antigen or IL-12 from macrophages)
Cytokines involved in granuloma formation?
IL-12
(facilitates granuloma formation in TB)
TNF-α
(Maintains granulomas in TB)
IFN-γ
(activates macrophages to induce granuloma formation, CGD chronic granulomatous disease treatment)
TNF-α Tumor necrosis factor-α effects?
secreted by?
Pro-inflammatory
- Phagocyte cell activation, WBC recruitment
- Endotoxic shock
- Activates endothelium → vascular leak
- Maintains granulomas in TB
- Cachexia in malignancy & chronic inflammation
(secreted by macrophages, NK cells)
Cytokines that can mediate sepsis?
IL-1
IL-6
TNF-α
TGF-β transforming growth factor-β effect?
secreted by?
Anti-inflammatory
- ↓ T and B cell
- ↓ hematopoiesis
- ↑ wound healing
- ↑ IgA
(secreted by T cells and B cells, platelets, macros, mast cells)
TNF-β effect?
secreted by?
Pro-inflammatory
-Chemotactic, phagocytosis, oncostatic, cytokines in phagocytes & tumor cells
(secreted by Th1, CTL)
Which cytokine is used as clinically to counteract the neutropenia following ablative chemotherapy?
G-CSF
granulocyte colony stimulating factor
GM-CSF
granulocyte macrophage colony stimulating factor
(both ↑ bone marrow granulocytes & pre-cursor macrophages)
IL-11 clinical use?
Thrombocytopenia prevention in cancer patients
↑ platelets
IL-2 clinical use?
Aldesleukin
Renal cell carcinoma
Malignant metastatic melanoma
(↑ lymphocytes, ↑ NKs)
Which cytokine is used for marrow recovery?
Why?
Sargramostim
(GM-CSF)
granulocyte macrophage colony stimulating factor
Filgrastim
(G-CSF)
granulocyte colony stimulating factor
↑ bone marrow granulocytes & pre-cursor macrophages
-used to counteract the neutropenia following ablative chemotherapy
Which cytokine is used in treatment of CGD (chronic granulomatous disease)?
IFN-γ
↑ macrophage activation (kill phagocytosed pathogen & granuloma formation) & ↑TNF
IFN-α effect?
secreted by?
Pro-inflammatory
-Anti-viral
(innate host defense; interfere with both RNA and DNA viruses; ↑ MHC expression to facilitate recognition of infected cells)
(secreted by macrophages, neutrophils, and some somatic cells)
Cytokines which inhibit viral replication?
IFN-α (hepatitis B & C, leukemias, melanoma)
IFN-β (multiple sclerosis)
Cytokine that induces class switch to IgE?
IL-4
IL-13
(stimulates proliferation & differentiation of activated B cells)
Cytokine that induces class switch to IgA?
IL-5
TGF-β
Aldesleukin clinical uses?
Aldesleukin (IL-2)
Renal cell carcinoma
Malignant metastatic melanoma
(↑ lymphocytes, ↑ NKs)
Sargramostim clinical use?
Sargramostim
(GM-CSF)
granulocyte macrophage colony stimulating factor
- marrow recovery
- used to counteract the neutropenia following ablative chemotherapy
(↑ bone marrow granulocytes & pre-cursor macrophages)
Filgrastim clinical use
Filgrastim
(G-CSF)
granulocyte colony stimulating factor
- marrow recovery
- used to counteract the neutropenia following ablative chemotherapy
(↑ bone marrow granulocytes & pre-cursor macrophages)
IFN-α clinical use?
(inhibits viral replication)
Chronic HBV, Hep B & C
Chronic granulomatous disease
Condyloma acuminatum (HPV anogenital warts)
(activating antitumor immunity) Hairy cell leukemia Malignant melanoma Kaposi sarcoma Renal cell carcinoma
Interferons common adverse effects?
Flu-like symptoms
Depression
Neutropenia
Myopathy
Interferon-induced autoimmunity
Which cytokine increases expression of ICAMs on endothelial cells?
IL-1
IFN-β clinical use?
Multiple sclerosis
↓ remission & ↓ severity of relapse in young adults
IFN-γ clinical use?
CGD (chronic granulomatous disease)
↑macrophage activation, ↑inflammatory response, ↑ROS inside phagocytic cells
Which cytokine has clinical use in multiple sclerosis?
IFN-β
Which cytokine has clinical use in hairy B cell leukemia?
IFN-α
Which cytokine has clinical use in hepatitis B & C infections?
IFN-α